Aims:
Age-related cognitive decline is well described, however the underlying
mechanisms remain poorly understood and available pre-clinical models provide
low predictive capacity for the clinic. Due to their similarity in brain
structure with humans, non-human primates are considered a valid model to
investigate cognitive deficits. The grey mouse lemur, Microcebus murinus, shows
age-related changes similar to those observed in aging humans. Some older mouse
lemurs show also evidence of Alzheimer’s pathology, such as amyloid plaques.The
aim of the present study is 1) to identify animals with age-related cognitive
deficit, and 2) to search for blood biomarkers (plasma A40 peptides and
insulin sensitivity) that correlate with cognitive dysfunction.

Methods: The spatial memory was evaluated in middle-aged
mouse lemurs (n=24) using the Barnes maze task and blood biomarkers were
analysed in all animals.

Results: the spatial reference tasks revealed a large
inter-individual variability in the middle-aged animals. Indeed, some of the
animals performed as well as younger ones whereas a subgroup of old animals
made more errors in the Barnes maze. Moreover, no significant correlation could
be found between cognitive deficit and amyloid peptides (A40). Interestingly,
the cognitive function was positively correlated with fasting plasma glucose
levels.

Conclusion: the spatial memory task results distinguish two different
populations in the mouse lemur: good and bad performers. The analyses of a
series of blood biomarkers showed interesting perspectives that may ultimately
lead to markers that can be associated with cognitive dysfunction in this
non-human primate species. The cognitive defect is associated with an increase
of fasting plasma glucose in middle-aged animals.